The broad objective of our work is to gain understanding of the physical mechanisms of the reactions between proteins and nucleic acids. We use as a model system the regulatory interactions of the lac operon of E. coli. One of the crucial questions that we want to address is the mechanism by which sequence-specific proteins reach their target site on the genome in the midst of a vast excess of other DNA sequences. A particular situation that we will also examine is the possible role of sequences which present striking analogies with and are situated near the target site. The influence that the binding of one protein at its site might have on the interaction of another protein at a nearby site will also be investigated. We propose experiments which should allow the distinction between the "linear diffusion" model and the "direct transfer" mechanism that have both been invoked to account for the very fast association of lac repressor and operator. We will measure the equilibrium and kinetic constants of the interaction of the CAP protein with its site on the lac promoter and the possible effect of this interaction on the stability of the repressor-operator complex.